In vitro modeling of hepatocellular carcinoma niche on decellularized tomato thorny leaves: a novel natural three-dimensional (3D) scaffold for liver cancer therapeutics

Abstract

Liver cancer is now one of the main causes leading to death worldwide. To achieve reliable therapeutic effects, it is crucial to develop efficient approaches to test novel anticancer drugs. Considering the significant contribution of tumor microenvironment to cell’s response to medications, in vitro 3D bioinspiration of cancer cell niches can be regarded as an advanced strategy to improve the accuracy and reliability of the drug-based treatment. In this regard, decellularized plant tissues can perform as suitable 3D scaffolds for mammalian cell culture to create a near-to-real condition to test drug efficacy. Here, we developed a novel 3D natural scaffold made from decellularized tomato hairy leaves (hereafter called as DTL) to mimic the microenvironment of human hepatocellular carcinoma (HCC) for pharmaceutical purposes. The surface hydrophilicity, mechanical properties, and topography measurement and molecular analyses revealed that the 3D DTL scaffold is an ideal candidate for liver cancer modeling. The cells exhibited a higher growth and proliferation rate within the DTL scaffold, as verified by quantifying the expression of related genes, DAPI staining, and SEM imaging of the cells. Moreover, prilocaine, an anticancer drug, showed a higher effectiveness against the cancer cells cultured on the 3D DTL scaffold, compared to a 2D platform. Taken together, this new cellulosic 3D scaffold can be confidently proposed for chemotherapeutic testing of drugs on hepatocellular carcinoma.

From Nature to Technology: Exploring the Potential of Plant-Based Materials and Modified Plants in Biomimetics, Bionics, and Green Innovations

“…A recent study reported the preparation of a new cellulosic 3D scaffold based on decellularized tomato thorny leaves which was recellularized with human hepatocellular carcinoma cancer cells (HepG2 cells) to mimic the tumor microenvironment for chemotherapeutic testing of prilocaine, an anticancer drug, on hepatocellular carcinoma [169]. This vegetal scaffold is an ideal candidate for liver cancer modeling.…”

In Vitro Cytocompatibility Assessment of Novel 3D Chitin/Glucan- and Cellulose-Based Decellularized Scaffolds for Skin Tissue Engineering

“…Esmaeili et al [24] decellularized the Alstroemeria flower stem and modified it with chitosan to fabricate a new scaffold for soft and hard tissue engineering. Very recently, Ahmadian et al [25] developed a novel 3D natural scaffold from decellularized tomato thorny leaves and used it as an ideal candidate for in vitro 3D hepatocellular carcinoma modeling.…”

Recent advances in scaffold based electrospun for breast cancer research

“…Recently, 3D scaffolds have emerged as an important tool for 3D in vitro tumor models and drug administration in cancer treatment. The in vitro model of a tumor has been used as an instrument for research into drug toxicity, the development of drugs, and anti‐cancer processes in addition to cancer cell biological processes, which include cancer growth, cell invasion, and metastasis‐related cancer cell movement 10,11 . 3D scaffolds are frequently used as drug‐releasing implants for in vivo cancer therapy and localized medication administration 12 …”